A new post-translational modification: What is the reason for protein lactosification?

Being bullied will leave a biochemical footprint in the brain
.

Protein lactosylation is a recently discovered post-translational modification of proteins, including the addition of lactose groups to lysine residues

Lactic acid is the final product of the glycolysis pathway, and its rate increases with increasing energy requirements
.

The body's lactic acid concentration, including the lactic acid concentration in the brain, will increase after exercise, but it is also related to other conditions

Recent studies have found that lysine lactosylation in macrophages is a new post-translational modification that can be stimulated by lactic acid
.

Japanese researchers are interested in whether protein lactosification also occurs in brain cells

Through biochemistry, cell culture, histology, and behavioral experiments in mice, the researchers confirmed that the proteins in the brain neurons of mice depend on neural activity for lactosylation
.

In the body, the brain area where this can be clearly determined is the prefrontal cortex (PFC)

The social stress experiment included placing a rat in a cage for 10 minutes, with a larger, more aggressive rat in the cage, allowing it to be strongly dominated
.

This was repeated for 10 days, every day the poor mouse was placed in the cage of another large mouse, and then the measurements were taken

Through mass spectrometry, the researchers identified 63 lactosylated proteins in the mouse PFC
.

Among these proteins, the lactosylation of H1 histones was significantly up-regulated after mice were exposed to a challenge environment

Histone modification mediates the epigenetic regulation of multiple genes
.

The lead author of the paper, Dr.
Hideo Hagihara, said: “Under stressful conditions, lactate-sensitive epigenetic changes may play a role in gene-mediated behavioral regulation

Obviously, the demonstration that nerve activation leads to the lactosylation of proteins (including histones) opens up a new field of neuroscience
.

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1. Hagihara H.
   et al.
   Protein lactylation induced by neural excitation.
   Cell Reports (2021).
   doi: https://doi.
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   celrep.
   2021.
   109820

2. Hagihara H, Shoji H, International Brain pH Project Consortium, Miyakawa T.
   Systematic analysis of brain lactate and pH levels in 65 animal models related to neuropsychiatric conditions.
   bioRxiv (2021).
   doi: https://doi.
   org/10.
   1101/2021.
   02 .
   02.
   428362